{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T15:50:50Z","timestamp":1770997850469,"version":"3.50.1"},"reference-count":55,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2017,9,14]],"date-time":"2017-09-14T00:00:00Z","timestamp":1505347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003052","name":"Ministry of Trade, Industry and Energy","doi-asserted-by":"publisher","award":["R0004490"],"award-info":[{"award-number":["R0004490"]}],"id":[{"id":"10.13039\/501100003052","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>Cardiovascular diseases such as acute myocardial infarction and heart failure accounted for the death of 17.5 million people (31% of all global deaths) in 2015. Monitoring the level of circulating N-terminal proBNP (NT-proBNP) is crucial for the detection of people at risk of heart failure. In this article, we describe a novel ultra-sensitive NT-proBNP test (us-NT-proBNP) that allows the quantification of circulating NT-proBNP in 30 min at 25 \u00b0C in the linear detection range of 7.0\u2013600 pg\/mL. It is a first report on the application of a fluorescence bead labeled detection antibody, DNA-guided detection method, and glass fiber membrane platform for the quantification of NT-proBNP in clinical samples. Limit of blank, limit of detection, and limit of quantification were 2.0 pg\/mL, 3.7 pg\/mL, and 7 pg\/mL, respectively. The coefficient of variation was found to be less than 10% in the entire detection range of 7\u2013600 pg\/mL. The test demonstrated specificity for NT-proBNP without interferences from bilirubin, intra-lipid, biotin, and hemoglobin. The serial dilution test for plasma samples containing various NT-proBNP levels showed the linear decrement in concentration with the regression coefficient of 0.980\u20130.998. These results indicate that us-NT-proBNP test does not suffer from the interference of the plasma components for the measurement of NT-proBNP in clinical samples.<\/jats:p>","DOI":"10.3390\/s17092116","type":"journal-article","created":{"date-parts":[[2017,9,14]],"date-time":"2017-09-14T10:04:49Z","timestamp":1505383489000},"page":"2116","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Ultra-Sensitive NT-proBNP Quantification for Early Detection of Risk Factors Leading to Heart Failure"],"prefix":"10.3390","volume":"17","author":[{"given":"Keum-Soo","family":"Song","sequence":"first","affiliation":[{"name":"Institute for Applied Chemistry and Department of Chemistry, Hallym University, Chuncheon 200-702, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satish","family":"Nimse","sequence":"additional","affiliation":[{"name":"Institute for Applied Chemistry and Department of Chemistry, Hallym University, Chuncheon 200-702, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mukesh","family":"Sonawane","sequence":"additional","affiliation":[{"name":"Institute for Applied Chemistry and Department of Chemistry, Hallym University, Chuncheon 200-702, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shrikant","family":"Warkad","sequence":"additional","affiliation":[{"name":"Institute for Applied Chemistry and Department of Chemistry, Hallym University, Chuncheon 200-702, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taisun","family":"Kim","sequence":"additional","affiliation":[{"name":"Institute for Applied Chemistry and Department of Chemistry, Hallym University, Chuncheon 200-702, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,9,14]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2017, June 09). Cardiovascular Diseases (CVDs), Factsheet. Available online: http:\/\/www.who.int\/mediacentre\/factsheets\/fs317\/en\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1056\/NEJMoa1406656","article-title":"Demographic and epidemiologic drivers of global cardiovascular mortality","volume":"372","author":"Roth","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_3","unstructured":"World Health Organization (2017, June 09). Available online: http:\/\/www.who.int\/nmh\/publications\/ncd_report_full_en.pdf."},{"key":"ref_4","first-page":"e29","article-title":"Heart disease and stroke statistics\u20142015 update: A Report from the American Heart Association","volume":"131","author":"Mozaffarian","year":"2015","journal-title":"Circulation"},{"key":"ref_5","first-page":"e38","article-title":"Heart disease and stroke statistics\u20142016 update: A Report from the American Heart Association","volume":"133","author":"Mozaffarian","year":"2016","journal-title":"Circulation"},{"key":"ref_6","unstructured":"(2017, June 09). Mortality Multiple Cause Micro-Data Files, Public-Use Data File and Documentation: NHLBI Tabulations, Available online: http:\/\/www.cdc.gov\/nchs\/data_access\/Vitalstatsonline.htm#Mortality_Multiple."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1161\/HHF.0b013e318291329a","article-title":"Forecasting the Impact of Heart Failure in the United States","volume":"6","author":"Heidenreich","year":"2013","journal-title":"Circ. Heart Fail."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1093\/eurheartj\/ehq163","article-title":"Age-dependent values of N-terminal pro-B-type natriuretic peptide are superior to a single cut-point for ruling out suspected systolic dysfunction in primary care","volume":"31","author":"Hildebrandt","year":"2010","journal-title":"Eur. Heart J."},{"key":"ref_9","first-page":"2388","article-title":"ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure","volume":"29","author":"Dickstein","year":"2008","journal-title":"Eur. Heart J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1586\/erc.10.3","article-title":"Systolic and diastolic left ventricular dysfunction: From risk factors to overt heart failure","volume":"8","author":"Kuznetsova","year":"2010","journal-title":"Expert Rev. Cardiovasc. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1016\/j.amjmed.2015.03.027","article-title":"American Heart Association\u2019s life\u2019s simple 7: Avoiding heart failure and preserving cardiac structure and function","volume":"128","author":"Folsom","year":"2015","journal-title":"Am. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.jacc.2013.05.019","article-title":"2013 ACCF\/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology Foundation\/American Heart Association Task Force on Practice Guidelines","volume":"62","author":"Yancy","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1016\/j.jacc.2007.09.021","article-title":"Natriuretic peptides","volume":"50","author":"Daniels","year":"2007","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1001\/archinte.167.5.483","article-title":"N-Terminal Pro\u2014B-type natriuretic peptide as a diagnostic test for ventricular dysfunction in patients with coronary disease","volume":"167","author":"Corteville","year":"2007","journal-title":"Arch. Intern. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1172\/JCI115146","article-title":"Brain natriuretic peptide as a novel cardiac hormone in humans. Evidence for an exquisite dual natriuretic peptide system, atrial natriuretic peptide and brain natriuretic peptide","volume":"87","author":"Mukoyama","year":"1991","journal-title":"J. Clin. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s10741-014-9442-y","article-title":"BNP and NT-proBNP as prognostic markers in persons with acute decompensated heart failure: A systematic review","volume":"19","author":"Santaguida","year":"2014","journal-title":"Heart Fail. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.ijcard.2015.01.082","article-title":"NT-proBNP is superior to BNP for predicting first cardiovascular events in the general population: The Heinz Nixdorf Recall Study","volume":"183","author":"Kara","year":"2015","journal-title":"Int. J. Cardiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1155\/2009\/837256","article-title":"Natriuretic peptides: Prediction of cardiovascular disease in the general population and high risk populations","volume":"26","author":"Hildebrandt","year":"2009","journal-title":"Dis. Markers"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e004675","DOI":"10.1136\/bmjopen-2013-004675","article-title":"The potential role of NT-proBNP in screening for and predicting prognosis in heart failure: A survival analysis","volume":"4","author":"Taylor","year":"2014","journal-title":"BMJ Open"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"245","DOI":"10.2147\/CIA.S98151","article-title":"The prognostic value of the plasma N-terminal pro-brain natriuretic peptide level on all-cause death and major cardiovascular events in a community-based population","volume":"11","author":"Zhu","year":"2016","journal-title":"Clin. Interv. Aging"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1016\/j.jacc.2008.11.009","article-title":"2009 Focused Update: ACCF\/AHA guidelines for the diagnosis and management of heart failure in adults: A report of the American College of Cardiology Foundation\/American Heart Association Task Force on Practice Guidelines","volume":"53","author":"Jessup","year":"2009","journal-title":"J. Am. Col. Cardiol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ajello, L., Coppola, G., Corrado, E., Franca, E.L., Rotolo, A., and Assennato, P. (2013). Diagnosis and treatment of asymptomatic left ventricular systolic dysfunction after myocardial infarction. ISRN Cardiol., 2013.","DOI":"10.1155\/2013\/731285"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/S0006-291X(89)80186-X","article-title":"Radioimmunoassay for brain natriuretic peptide (BNP) detection of BNP in canine brain","volume":"158","author":"Itoh","year":"1989","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_24","first-page":"283","article-title":"A specific and highly sensitive radioimmunoassay of human brain natriuretic peptide","volume":"39","author":"Togashi","year":"1991","journal-title":"Rinsho Byori."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1515\/CCLM.2002.130","article-title":"Comparative measurement of N-terminal pro-brain natriuretic peptide and brain natriuretic peptide in ambulatory patients with heart failure","volume":"40","author":"Masson","year":"2002","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1177\/1040638715588330","article-title":"Analytical validation of an immunoassay for the quantification of N-terminal pro-B-type natriuretic peptide in feline blood","volume":"27","author":"Mainville","year":"2015","journal-title":"J. Vet. Diagn. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.clinbiochem.2012.11.022","article-title":"Comparison of immunoassays for NTproBNP conducted on three analysis systems: Milliplex, Elecsys and RIA","volume":"46","author":"Lewis","year":"2013","journal-title":"Clin. Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.bios.2016.08.109","article-title":"An ultrasensitive electrochemiluminescence immunosensor for NT-proBNP based on self-catalyzed luminescence emitter coupled with PdCu@carbon nanohorn hybrid","volume":"87","author":"Liu","year":"2017","journal-title":"Biosens. Bioelectron."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.aca.2013.04.039","article-title":"Disposable amperometric magnetoimmunosensor for the sensitive detection of the cardiac biomarker amino-terminal pro-B-type natriuretic peptide in human serum","volume":"784","author":"Campuzano","year":"2013","journal-title":"Anal. Chim. Acta"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7716","DOI":"10.1039\/c1cc12721g","article-title":"9G DNAChip: A platform for the efficient detection of proteins","volume":"47","author":"Song","year":"2011","journal-title":"Chem. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3773","DOI":"10.1039\/C7AY00521K","article-title":"Multiplex detection of cardiac biomarkers","volume":"9","author":"Sonawane","year":"2017","journal-title":"Anal. Methods"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1039\/c3cc39231g","article-title":"A new platform for a convenient genotyping system","volume":"49","author":"Song","year":"2013","journal-title":"Chem. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"19162","DOI":"10.3390\/s141019162","article-title":"HPV Genotyping 9G membrane test: A point-of-care diagnostic platform","volume":"14","author":"Song","year":"2014","journal-title":"Sensors"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3818","DOI":"10.1016\/j.bios.2011.02.036","article-title":"A fluoro-microbead guiding chip for simple and quantifiable immunoassay of cardiac troponin I (cTnI)","volume":"26","author":"Song","year":"2011","journal-title":"Biosens. Bioelectron."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6534","DOI":"10.1021\/ac070484i","article-title":"Self-directed and self-oriented immobilization of antibody by protein G-DNA conjugate","volume":"79","author":"Jung","year":"2007","journal-title":"Anal. Chem."},{"key":"ref_36","unstructured":"Tholen, D.W., Linnet, K., Kondratovich, M., Armbruster, D.A., Garrett, P.E., Jones, R.L., Kroll, M.H., Lequin, R.M., Pankratz, T.J., and Scassellati, G.A. (2004). Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline, NCCLS. NCCLS Document EP17-A."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1373\/clinchem.2003.026815","article-title":"Evaluation of imprecision for cardiac troponin assays at low-range concentrations","volume":"50","author":"Panteghini","year":"2004","journal-title":"Clin. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.1373\/clinchem.2005.052886","article-title":"Validation of the 99th percentile cutoff independent of assay imprecision (CV) for cardiac troponin monitoring for ruling out myocardial infarction","volume":"51","author":"Apple","year":"2005","journal-title":"Clin. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.cccn.2003.08.016","article-title":"Multicenter evaluation of the Roche NT-proBNP assay and comparison to the biosite triage BNP assay","volume":"338","author":"Yeo","year":"2003","journal-title":"Clin. Chim. Acta"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1515\/CCLM.2006.215","article-title":"Multicentre evaluation of a new point-of-care test for the determination of NT-proBNP in whole blood","volume":"44","author":"Zugck","year":"2006","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s00392-009-0108-z","article-title":"Natriuretic peptides in the detection of preclinical diastolic or systolic dysfunction","volume":"99","author":"Luers","year":"2010","journal-title":"Clin. Res. Cardiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1161\/CIRCULATIONAHA.115.017298","article-title":"N-Terminal Pro-Brain Natriuretic Peptide and Heart Failure Risk Among Individuals With and Without Obesity: The Atherosclerosis Risk in Communities (ARIC) Study","volume":"133","author":"Ndumele","year":"2016","journal-title":"Circulation"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.1056\/NEJMoa055373","article-title":"Multiple biomarkers for the prediction of first major cardiovascular events and death","volume":"355","author":"Wang","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.jacc.2009.07.069","article-title":"Dynamic cardiovascular risk assessment in elderly people. The role of repeated N-terminal pro-B-type natriuretic peptide testing","volume":"55","author":"Defilippi","year":"2010","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1157\/13125520","article-title":"Usefulness of NT-proBNP level for diagnosing left ventricular hypertrophy in hypertensive patients. A cardiac magnetic resonance study","volume":"61","author":"Morillas","year":"2008","journal-title":"Rev. Esp. Cardiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.cardfail.2005.04.022","article-title":"Diagnostic and prognostic performance of N-terminal ProBNP in primary care patients with suspected heart failure","volume":"11","author":"Gustafsson","year":"2005","journal-title":"J. Card. Fail."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1161\/CIRCHEARTFAILURE.111.964841","article-title":"Prediction of incident heart failure in general practice: The Atherosclerosis Risk in Communities (ARIC) Study","volume":"5","author":"Agarwal","year":"2012","journal-title":"Circ. Heart Fail."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1093\/eurheartj\/ehw128","article-title":"2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"37","author":"Ponikowski","year":"2016","journal-title":"Eur. J. Heart Fail."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Dietl, A., Stark, K., Zimmermann, M.E., Meisinger, C., Schunkert, H., Birner, C., Maier, L.S., Peters, A., Heid, I.M., and Luchner, A. (2016). NT-proBNP Predicts Cardiovascular Death in the General Population Independent of Left Ventricular Mass and Function: Insights from a Large Population-Based Study with Long-Term Follow-Up. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0164060"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.amjcard.2007.11.017","article-title":"Amino-terminal Pro\u2014B-type natriuretic peptide testing for the diagnosis or exclusion of heart failure in patients with acute symptoms","volume":"101","author":"Januzzi","year":"2008","journal-title":"Am. J. Cardiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.2169\/internalmedicine.46.0188","article-title":"Non-specific activities against ruthenium crosslinker as a new cause of assay interference in an electrochemilluminescent immunoassay","volume":"46","author":"Ando","year":"2007","journal-title":"Intern. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1515\/cclm-2016-0786","article-title":"Immunoassay interference caused by heterophilic antibodies interacting with biotin","volume":"55","author":"Vos","year":"2017","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1258\/acb.2008.008224","article-title":"A patient with pseudo-Addison\u2019s disease and falsely elevated thyroxine due to interference in serum cortisol and free thyroxine immunoassays by two different mechanisms","volume":"46","author":"Saleem","year":"2009","journal-title":"Ann. Clin. Biochem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1515\/cclm-2016-0140","article-title":"Utility of dilution tests in investigating interference in the free thyroxine assay","volume":"55","author":"Oostendorp","year":"2017","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.3390\/s130101353","article-title":"Nucleic Acids for Ultra-Sensitive Protein Detection","volume":"13","author":"Janssen","year":"2013","journal-title":"Sensors"}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/17\/9\/2116\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:44:57Z","timestamp":1760208297000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/17\/9\/2116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,14]]},"references-count":55,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2017,9]]}},"alternative-id":["s17092116"],"URL":"https:\/\/doi.org\/10.3390\/s17092116","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,14]]}}}